依枯草菌素是由氨基酸和脂肪酸组成的环状脂肽，能够抑制多种产毒真菌的生长和产毒，在食品防腐保鲜方面应用前景广阔。但因其结构复杂，大规模合成和生产困难。申请人前期研究发现，依枯草菌素的抗真菌活性与氨基酸和脂肪酸结构组成密切相关，但决定其抗真菌活性的关键结构及其作用机制尚不清楚。阐明依枯草菌素抗真菌活性的关键结构与作用机制是指导其合成和生产的重要前提。为此，本项目将以脂肪酸和肽环结构不同的依枯草菌素A（IA）为材料，（1）研究不同结构IA的抗真菌活性，明确决定IA抗真菌作用的关键结构；（2）分析关键结构与抗真菌作用靶点（麦角固醇或磷脂）在体外和真菌细胞内的结合能力，揭示关键结构识别、结合靶点的分子机制；（3）明确关键结构结合靶点后的抗真菌作用途径与机制；最终阐明依枯草菌素识别、结合靶点的关键结构及其分子作用机制。研究将为简化和调控依枯草菌素的合成提供理论依据，同时为开发新型抗真菌剂提供借鉴。

Iturins is a kind of cyclic lipopeptides composed of amino acids and fatty acids. They have high inhibitory effect on the growth and mycotoxin production of a variety of toxin-producing fungi, and show vast application prospect in food preservation and antisepsis. Because of the complex structure, the large-scale synthesis and production of iturins are difficult. Our previous study showed that the antifungal activity of iturins was associate with the amino acids and fatty acids composition, but their key antifungal activity structure and mechanism of action are unclear. It is an important prerequisite to confirm the key antifungal activity structure and its mechanism for guiding the synthesis and production of iturins. This project uses iturin A with different fatty acids and peptide structures (all of above shorten for IA) as materials, firstly, according to the antifungal activity of IA, identify the key antifungal structure of IA. Secondly, through analysis of the combination effect between the key structure and the antifungal targets of ergosterol and phospholipids in vitro and fungal cells, reveal the molecular mechanism of the key structures for recognizing and combing the targets. Thirdly, confirm the antifungal effect and mechanism of the key structure after combination with targets. And finally, clarify the key structure of iturins for recognition and combination with the targets and its molecular mechanism. This study will provide theoretical basis for simplifying and regulating the synthesis of iturins and moreover serve as a reference for the development of new antifungal agents.